DESCRIPTION: The principal investigator has been instrumental in modifying the Hu-SCID mouse model such that it exhibits high levels of virus replication. A series of experiments are proposed in these Hu-SCID mice to address the following questions: 1. Where does the HIV present in the plasma come from? 2. Whatfactors contribute to the level of plasma viremia? 3. Why does the tropism of HIV shift from M-tropic during infection? 4. Is there a reservoir where in HIV can evade multidrug therapy? 5. What factors contribute to the in vivo development of drug-resistant isolates? 6. Can acute provision of drug therapy abort HIV infection? 7. Can the course of HIV infection be modified by cytokine or chemokine treatment? In addition, they will explore the capacity of mice that they have recently developed that are transgenic for human CD4 and CCR5 for studying the pathogenesis of HIV infection.